Peripheral arterial disease and claudication — practice case: from claudication to CLTI

Presentation

Practice case (not a real patient). A 68-year-old man in Australia with type 2 diabetes and chronic kidney disease has had calf pain on walking for a year, relieved by rest. He stopped smoking 5 years ago.^[1] His resting ABI is 1.46 in both legs. His toe–brachial index is 0.52 on the right and 0.81 on the left. His LDL-C is 2.4 mmol/L on atorvastatin, he takes metformin, and his eGFR is 48 mL/min/1.73 m². He has no history of stroke, TIA, intracranial haemorrhage or bleeding, and no acute coronary syndrome.^[1]

Step 1 — Is this PAD?

Discussion:

• ESC 2024 says the term non-compressible arteries should be used for an ABI >1.40, and with non-compressible ankle arteries or an ABI >1.40, additional methods such as toe pressure, TBI or Doppler waveform analysis are recommended (Class I, Level B).^[1]
• The usual pathological threshold for the TBI is ≤0.70, so the right TBI of 0.52 is abnormal.^[1]
• With diabetes or renal failure, measuring toe pressure or TBI is recommended if the resting ABI is normal (Class I, Level C).^[1]
• Duplex ultrasound is recommended as the first-line imaging method to confirm PAD lesions (Class I, Level C).^[1]

Step 2 — Treating his cardiovascular risk

Discussion:

• Statins are recommended in all patients with PAD (ESC 2024, Class I, Level A), with an ultimate LDL-C goal of <1.4 mmol/L and a >50% reduction from baseline (Class I, Level A); at 2.4 mmol/L on a statin, adding ezetimibe is indicated (Class I, Level B).^[1]
• With type 2 diabetes, an SGLT2 inhibitor and a GLP-1 receptor agonist with proven cardiovascular benefit are each recommended to reduce cardiovascular events, independent of HbA1c and other glucose-lowering drugs (Class I, Level A).^[1]
• Aspirin alone (75–160 mg once daily) or clopidogrel alone (75 mg once daily) is recommended to reduce MACE in symptomatic PAD (Class I, Level A).^[1]
• Diabetes and an eGFR <60 mL/min/1.73 m² are each listed by ESC 2024 as high ischaemic risk, and he has none of its high-bleeding-risk features, so rivaroxaban 2.5 mg twice daily plus aspirin 100 mg once daily should be considered (Class IIa, Level A).^[1]
• Supervised exercise training is recommended in symptomatic PAD (Class I, Level A).^[1]

Step 3 — Two years later

He now has right forefoot pain at night, eased by hanging the leg over the bed, and a toe ulcer that has not healed for 4 weeks. His right toe pressure is 26 mmHg. There is spreading redness around the ulcer.^[1]

• ESC 2024 says CLTI should be considered with ischaemic rest pain, a non-healing lower-limb wound of ≥2 weeks or lower-limb gangrene, and a toe pressure <30 mmHg may be used to guide diagnosis.^[1]
• Early recognition of CLTI and referral to the vascular team are recommended for limb salvage (Class I, Level C); management by a vascular team is recommended (Class I, Level C).^[1]
• Offloading mechanical tissue stress (Class I, Level C) and treating infection with antibiotics (Class I, Level C) are recommended; lower-limb exercise training is not recommended with CLTI and wounds (Class III, Level C).^[1]
• The Australian guideline on PAD in diabetes-related foot disease (abstract held) says further vascular imaging and possible need for revascularisation should be considered for all patients with a non-healing diabetes-related foot ulcer (DFU) irrespective of bedside results (no grade given in the abstract).^[13]

Step 4 — Revascularization

Imaging shows infra-popliteal disease. He has a good great saphenous vein, and his peri-operative risk is judged low.^[1][10]

• ESC 2024 recommends revascularization as soon as possible (Class I, Level B), with autologous vein as the preferred conduit for infra-inguinal bypass (Class I, Level B), and an individual risk assessment of endovascular versus surgical revascularization by a multidisciplinary vascular team (Class I, Level C).^[1]
• With good autologous veins and low surgical risk (<5% peri-operative mortality, >50% 2-year survival), infra-inguinal bypass may be considered (Class IIb, Level B); endovascular first-line therapy may be considered, especially with increased surgical risk or inadequate vein (Class IIb, Level B).^[1]
• BEST-CLI (1830 patients with CLTI and infrainguinal PAD, international randomised trial; median follow-up 2.7 years in cohort 1) found a significantly lower incidence of a major adverse limb event or death with surgery than with endovascular therapy in patients with an adequate great saphenous vein (42.6% vs. 57.4%; HR 0.68).^[10]
• BASIL-2 (345 patients with CLTI needing infra-popliteal revascularization, enrolled July 2014 to November 2020; open-label randomised trial in the UK, Sweden and Denmark) found that a best endovascular treatment first strategy, compared with a vein bypass first strategy, was associated with better amputation-free survival, largely driven by fewer deaths in the best endovascular treatment group.^[11]

Step 5 — After bypass

He has a vein bypass, the ulcer heals, and he has no bleeding risk features.^[1]

• After lower-limb revascularization with non-high bleeding risk, rivaroxaban 2.5 mg twice daily plus aspirin 100 mg once daily should be considered (ESC 2024, Class IIa, Level B).^[1]
• VOYAGER PAD (6564 patients with PAD after lower-extremity revascularization, double-blind) reported fewer composite limb and cardiovascular events with rivaroxaban plus aspirin than placebo plus aspirin (Kaplan-Meier estimates at 3 years 17.3% vs. 19.9%; HR 0.85), with significantly more ISTH major bleeding.^[7]
• Regular follow-up after CLTI revascularization is recommended (Class I, Level C); ESC 2024 text advises clinical examination, ABI or TBI and duplex within 4–6 weeks and then at 3, 6, 12 and 24 months after bypass.^[1]
• ESC 2024 puts the first-year incidence of vein graft stenosis at 20%.^[1]

Examiner criteria

• Pass: does not trust an ABI >1.40 and uses the TBI; treats LDL-C towards <1.4 mmol/L, starts SGLT2 inhibitor or GLP-1 receptor agonist therapy, antiplatelet therapy and supervised exercise; recognises CLTI and refers early; offloads and treats infection; revascularizes as soon as possible with a vein conduit; sets follow-up after bypass.^[1]
• Fail: calls the leg normal on an ABI of 1.46, prescribes exercise training for a patient with CLTI and a wound (ESC 2024: not recommended, Class III, Level C), or delays revascularization.^[1]